Triacylglycerols are quantitatively the most important storage form of energy in eukaryotes. Triglyceride synthesis is thought to occur primarily through acyl CoA:diacylglycerol transferase (DGAT), a microsomal enzyme. Diacylglycerol acyl-transferase (DGAT; acyl CoA:diacylglycerol acyltransferase; EC 2.3.1.20) is a ubiquitous enzyme that catalyzes the synthesis of triglycerides by adding a fatty acid to diacylglycerol. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol, and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism, such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. Cases et al. (1998) Proc. Natl. Acad. Sci. USA 95:13018-13023.
Abnormal fat storage causes, or is related to, a variety of debilitating, and often lethal, conditions As one example, obesity, generally defined as a condition of being 20% or more over ideal body weight, affects an estimated 34 million Americans, and is a major cause of death in the Unites States. Morbid obesity, a much more severe form of obesity in which a person is 100 or more pounds overweight, affects an estimated four million Americans. One important consequence of obesity is maturity-onset (Type II) diabetes. Obesity is also linked to, or increases the risk of, hypertension, atherosclerosis, and myocardial infarction, as well as other serious disorders. Hypertension alone affects approximately 50 million Americans, and increases the risk of heart disease and stroke, which are leading causes of death among Americans. The profound negative health and social consequences of obesity have provided the impetus for development of a large number of drugs for control of this condition. Bray and Greenway (1999) Endocrinol. Rev. 20:805-875. While several genes and mutations have been identified that contribute to obesity and other common metabolic disorders, they represent a small fraction of the genetic causes of obesity. Chagnon et al. (2000) Obesity Res. 8:89-117; and Barsh et al. (2000) Nature 404:644-651.
Despite advances in detecting mutations and genes associated with obesity, obesity continues to exert adverse effects on human health. Thus, there is a need in the art for identification of additional information regarding genes and gene mutations associated with obesity. Such information is crucial for identifying individuals who have a propensity toward becoming obese, and for identifying new therapeutic targets for control of obesity. The present invention addresses this need by providing polymorphisms associated with conditions associated with DGAT activity, including, e.g., obesity.